Protoporphyrin IX accumulation disrupts mitochondrial dynamics and function in ABCG2‐deficient hepatocytes
Copyright policy )Protoporphyrin IX accumulation disrupts mitochondrial dynamics and function in ABCG2‐deficient hepatocytes
Targeted inhibition of multidrug ABCG2 transporter is believed to improve cancer therapeutics. However, the consequences of ABCG2 inhibition have not been systematically evaluated since ABCG2 is expressed in several organs including the liver. Here, we demonstrate that ABCG2‐deficient hepatocytes have increased amounts of fragmental mitochondria accompanied by disruption of mitochondrial dynamics and functions. This disruption was due to ABCG2 knockout elevating intracellular protoporphyrin IX, which led to upregulation of DRP‐1‐mediated mitochondrial fission. The finding that ABCG2 deficiency can generate dysfunctional mitochondria in hepatocytes raises concerns regarding the systematic use of ABCG2 inhibitor in cancer patients.
- National Taiwan University of Arts Taiwan
- Taipei Medical University Taiwan
- Academia Sinica Taiwan
- National Defense Medical Center Taiwan
- Chang Gung University Taiwan
Mice, Knockout, Protoporphyrin IX, Mitochondrial fission, ABCG2, Protoporphyrins, Mitochondria, Liver, Mitochondrial Dynamics, Mice, Hepatocytes, ATP Binding Cassette Transporter, Subfamily G, Member 2, Animals, Hepatocyte, ATP-Binding Cassette Transporters, Cells, Cultured, Glycogen
Mice, Knockout, Protoporphyrin IX, Mitochondrial fission, ABCG2, Protoporphyrins, Mitochondria, Liver, Mitochondrial Dynamics, Mice, Hepatocytes, ATP Binding Cassette Transporter, Subfamily G, Member 2, Animals, Hepatocyte, ATP-Binding Cassette Transporters, Cells, Cultured, Glycogen
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